A 74-year-old man with a history of atrial fibrillation and coronary artery disease came to see you in clinic for follow up. He received drug-eluting stents about 1.5 years ago and is being treated with rivaroxaban for anticoagulation and aspirin. He reports no symptoms of gastrointestinal bleeding and does not smoke. His vital signs show normotensive blood pressure readings and he has a body-mass index of 25 kg/m2. His recent hemoglobin A1c was normal and his creatinine clearance was 63 mL/min.
How should you manage antithrombotic therapy in this patient?
In patients with atrial fibrillation, the current guidelines recommend anticoagulation with vitamin K antagonists or direct oral anticoagulants to reduce thromboembolic events because it has been shown to be superior to antiplatelet therapy.
In patients with stable coronary artery disease, daily aspirin or dual antiplatelet therapy (aspirin plus P2Y12 inhibitor therapy) is recommended for 1–12 months to reduce cardiovascular events.
In patients with atrial fibrillation and recent acute coronary syndrome or who recently required percutaneous coronary intervention, the recent AUGUSTUS trial showed that a direct oral anticoagulant (apixaban) and a P2Y12 inhibitor without aspirin reduced the risk of bleeding without significantly increasing adverse events.
What remains unclear, however, is the optimal antithrombotic regime for patients with both atrial fibrillation and stable coronary artery disease.
In the randomized AFIRE trial recently published in NEJM, Yasuda et. al. compared rivaroxaban monotherapy versus combination therapy with rivaroxaban plus aspirin or a P2Y12 inhibitor in patients with atrial fibrillation and stable coronary artery disease. Monotherapy with a direct oral anticoagulant was associated with lower rates of mortality and major bleeding than combination in patients with atrial fibrillation and stable coronary artery disease.
In the above clinical scenario of a patient with stable coronary artery disease with drug-eluting stents placed more than one year ago and atrial fibrillation, discontinuing aspirin and keeping the patient on monotherapy rivaroxaban would be the optimal drug regime.
The following NEJM Journal Watch summary explains the study and results in more detail:
Clarity on Antithrombotic Therapy for Atrial Fibrillation plus Chronic CAD
Mark S. Link, MD reviewing Yasuda S et al. N Engl J Med 2019 Sep 2
Finally, we can be sure that anticoagulation without an antiplatelet agent is best for patients with atrial fibrillation and chronic coronary artery disease.
Several randomized, controlled trials (e.g., RE-DUAL; NEJM JW Cardiol Aug 27 2017; [e-pub] and N Engl J Med 2017; 377:1513) have shown that for most patients with atrial fibrillation (AF), the standard of care for the first year after percutaneous coronary intervention (PCI) is anticoagulation plus a single antiplatelet agent. However, pertinent data more than 1 year after PCI have been limited. AFIRE, a randomized trial from Japan (NCT02642419), provides clarity on optimal antithrombotic therapy in this population.
Researchers randomized 2236 patients with AF who had undergone PCI or coronary artery bypass grafting at least 1 year earlier, or who had a history of angiographically confirmed coronary artery disease (CAD; stenosis ≥50%) not requiring revascularization, to receive either rivaroxaban alone or rivaroxaban plus aspirin or a P2Y12 inhibitor. The trial was stopped early because of increased mortality in the combination-therapy arm.
Incidence of the primary efficacy endpoint — stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, or death from any cause — was noninferior with rivaroxaban, compared with combination therapy (4.14% vs. 5.75% per patient-year, respectively). Death from any cause, a prespecified secondary endpoint, was significantly less common with rivaroxaban alone than with combination therapy (1.85% vs. 3.37% per patient-year) — as was major bleeding (1.62% vs. 2.76% per patient-year, respectively).
Comment: We finally have clarity: Patients with AF and chronic CAD should receive only anticoagulation, not antiplatelet agents. Although existing guidelines had made this recommendation, the evidence base was slim, and many patients were nevertheless kept on anticoagulation plus an antiplatelet agent. These new data from AFIRE should help to end that practice. Notably, AFIRE used a 15-mg rivaroxaban dose for patients with normal renal function, but that dose in typical Japanese patients yields a serum level equivalent to 20-mg rivaroxaban in typical white patients — a fact to bear in mind when individualizing treatment.
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James Yeh, MD MPH is an internist and assistant in medicine at the Massachusetts General Hospital and an instructor in medicine at Harvard Medical School. His clinical and academic interests are in evidence-based medicine, medical education, continuing medical education, cardiopulmonary diseases, cardiovascular risk reduction, critical illness, care transition, polypharmacy, and health communication. He was a NEJM editorial fellow in 2015-2016.